Using immunocytochemistry we have given evidence that there are several systems in the brain in which there are coexisting transmitters, i.e., more than one transmitter in a single cell. In the mesencephalon, cholecystokinin (CCK) and dopamine (DA) exist in cells of the ventral tegmentum and lateral substantia nigra zona compacta, and in the periaqueductal grey, CCK and substance P coexist in neurons. Electrophysiological studies have shown that CCK is a potent excitatory agent in substantia nigra and this excitation is limited to areas in which CCK and DA coexist. In contrast, enkephalins excite DA cells by acting indirectly on cells of the zona reticulata which normally inhibit DA cell activity.